CHEN Guan-xin, WEN Bin, SUN Hai-tao, et al. Effect of Biejiajian Wan on NF-B Signaling Pathway in Rat Hepatic Fibrosis Model Induced by CCl[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(10): 161-167.
DOI:
CHEN Guan-xin, WEN Bin, SUN Hai-tao, et al. Effect of Biejiajian Wan on NF-B Signaling Pathway in Rat Hepatic Fibrosis Model Induced by CCl[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(10): 161-167. DOI: 10.13422/j.cnki.syfjx.20180834.
Effect of Biejiajian Wan on NF-B Signaling Pathway in Rat Hepatic Fibrosis Model Induced by CCl
Objective: To study the inhibitory effects of Biejiajian Wan on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats and its effect on nuclear factor-kappa B (NF-κB) signaling pathway modules and target genes
in order to discuss the mechanism of Biejiajian Wan's anti-hepatic fibrosis. Method: CCl4 was used to duplicate the rat model of hepatic fibrosis. Biejiajian Wan solution was administered by gavage. At the end of 8 weeks
blood sampling was collected from aorta abdominalis. Hepatic tissues were taken for detecting indexes. Hematoxylin-eosin (HE) staining was used to observe the changes of livers' pathomorphology; enzyme linked immunosorbent assay (ELISA) was applied to detect four indicators of hepatic fibrosis
matrix metalloproteinases (MMP)-2
MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1 expressions in rat serum. Immunohistochemistry was applied to measure p65 and transforming growth factor (TGF)-β1 expressions. Western blot was used to detect p65
inhibitor of NF-κB (IκB) α
inhibitor of NF-κB kinase (IKK) α/β and TGF-β1 expressions. Result: Pathological results showed that the hepatic lobule in the model group was destroyed
with serious proliferation of fibrous tissues. In the treatment group of Biejiajian Wan
both necrocytosis and proliferation of fibrous tissues were obviously reduced
while fibrous septum was thin. Compared with the model group
four indicators of hepatic fibrosis and TIMP-1 contents in the treatment group of Biejiajian Wan were significantly reduced (P<0.05)
while MMP-2 and MMP-9 contents were obviously increased (P<0.05). Immunohistochemical results indicated that p65 and TGF-β1 expressions of hepatic tissues in the treatment group of Biejiajian Wan were obviously reduced compared with those of the model group. According to Western blot results
compared with the model group
p65 and TGF-β1 protein expressions of hepatic tissues in the treatment group of Biejiajian Wan were significantly decreased (P<0.05)
while IκBα protein expression was obviously increased (P<0.05). IKKα/β had no significantly changes. Conclusion: Biejiajian Wan can significantly alleviate rat hepatic fibrosis induced by carbon tetrachloride and retard the development. Biejiajian Wan can inhibit p65 expressions
so as to block NF-κB signaling pathway
reduce synthesis of downstream target genes TIMP-1 and TGF-β1
up-regulate MMP-2 and MMP-9 expressions
and further accelerate degradation of extracellular matrix.